AP Biology Thanks as always to Kim Foglia

Beyond Mendel’s Lawsof Inheritance

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Extending Mendelian genetics Mendel worked with a simple system

peas are genetically simple most traits are controlled by a single gene each gene has only 2 alleles, 1 of which

is completely dominant to the other

The relationship between genotype & phenotype is rarely that simple

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Incomplete dominance Heterozygote shows an intermediate,

blended phenotype example:

RR = red flowers rr = white flowers Rr = pink flowers

make 50% less color

RR Rr rr

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Incomplete dominancetrue-breeding

red flowerstrue-breeding white flowers

XP

100%

100% pink flowers

F1generation(hybrids)

self-pollinate

25%white

F2generation

25%red 1:2:1

50%pink

It’s likeflipping 2 pennies!

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Incomplete dominance

CR CW

male / sperm

CR

CW

fem

ale

/ eg

gs CRCR

CRCW CWCW

CRCW

25%

1:2:1

25%

50%

25%

1:2:1

%genotype

%phenotype

CRCR

CRCW

CRCW

CWCW

25%

50%

CRCW x CRCW

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Co-dominance 2 alleles affect the phenotype equally &

separately not blended phenotype example: ABO blood groups 3 alleles

IA, IB, i IA & IB alleles are co-dominant to each other

both antigens are produced both IA & IB are dominant to i allele

produces glycoprotein antigen markers on the surface of red blood cells

AP Biology

Genetics of Blood type

pheno-type

genotypeantigenon RBC

antibodiesin blood

donationstatus

A IA IA or IA itype A antigens

on surface of RBC

anti-B antibodies __

B IB IB or IB itype B antigens

on surface of RBC

anti-A antibodies __

AB IA IB

both type A & type B antigens

on surface of RBC

no antibodiesuniversal recipient

O i ino antigens on surface

of RBC

anti-A & anti-B antibodies

universal donor

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Blood compatibility Matching compatible blood groups

critical for blood transfusions A person produces antibodies against

antigens in foreign blood wrong blood type

donor’s blood has A or B antigen that is foreign to recipient

antibodies in recipient’s blood bind to foreign molecules

cause donated blood cells to clump together can kill the recipient

Karl Landsteiner(1868-1943)

1901 | 1930

Charles Drew(1904-1950)

African AmericanBlood Bank

Pioneer

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Blood donation

clotting clotting

clotting clotting

clotting clotting clotting

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Pleiotropy Most genes are pleiotropic

one gene affects more than one phenotypic character wide-ranging effects due to a single gene dwarfism (achondroplasia) gigantism (acromegaly)

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Acromegaly: André the Giant

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Aa x aa

Inheritance pattern of Achondroplasia

a a

A

a

A a

A

a

Aa x Aa

Aa

aa aa

Aa

50% dwarf:50% normal or 1:1

AA

aa

Aa

67% dwarf:33% normal or 2:1

Aa

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Epistasis

B_C_B_C_

bbC_bbC_

_ _cc_ _cc

How would you know thatdifference wasn’t random chance?

Chi-square test!

One gene completely masks another gene coat color in mice = 2 separate genes

C,c: pigment (C) or no pigment (c)

B,b: more pigment (black=B) or less (brown=b)

cc = albino, no matter B allele

9:3:3:1 becomes 9:3:4

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Epistasis in Labrador retrievers 2 genes: (E,e) & (B,b)

pigment (E) or no pigment (e) pigment concentration: black (B) to brown (b)

E–B–E–bbeeB–eebb

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Epistasis in grain color

9/16 purple7/16 white

F1 generation

All purple(AaBb)

X

Eggs

White(aaBB)

White(AAbb)

F2 generation

A = enzyme 1+

B = enzyme 2

purple color(anthocyanin)

AB

AB Ab aB ab

Ab

aB

ab

AABB

AABb

AaBB

AaBb

AABb

AAbb

AaBb

Aabb

AaBB

AaBb

aaBB

aaBb

AaBb

Aabb

aaBb

aabb

Sperm

9:7

9:3:3:1

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Polygenic inheritance Some phenotypes determined by

additive effects of 2 or more genes on a single character phenotypes on a continuum human traits

skin color height weight eye color intelligence behaviors

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Skin color: AlbinismJohnny & Edgar Winter

albinoAfricans

However albinism can be inherited as a single gene trait

melanin = universal brown color

tyrosine melaninalbinism

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OCA1 albino Bianca Knowlton

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Sex linked traits Genes are on sex chromosomes

as opposed to autosomal chromosomes first discovered by T.H. Morgan at Columbia U. Drosophila breeding

good genetic subject prolific

2 week generations

4 pairs of chromosomes

XX=female, XY=male

1910 | 1933

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autosomal

chromosomes

sexchromosomes

Classes of chromosomes

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Huh!Sex matters?!

F2generation

100%red-eye female

50% red-eye male50% white eye male

Discovery of sex linkage

P X

F1generation(hybrids)

100%red eye offspring

true-breeding white-eye male

true-breedingred-eye female

AP Biology

RR rr

What’s up with Morgan’s flies?

x

r r

R

R

Rr

Rr Rr

Rr

100% red eyes

Rr Rr

x

R r

R

r

RR

Rr rr

Rr

3 red : 1 white

Doesn’t workthat way!

AP Biology

In humans & other mammals, there are 2 sex chromosomes: X & Y 2 X chromosomes

develop as a female: XX gene redundancy,

like autosomal chromosomes an X & Y chromosome

develop as a male: XY no redundancy

Genetics of Sex

X Y

X

X

XX

XY

XY

50% female : 50% maleXX

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XRXR XrY

What’s up with Morgan’s flies?

x

Xr Y

XR

100% red eyes

XR

XRXr XRY

XRYXRXr

x

XRXr XRY

XR Y

XR

Xr

XRXr

XRYXRXR

XrY100% red females50% red males; 50% white males

BINGO!

AP Biology

Genes on sex chromosomes Y chromosome

few genes other than SRY sex-determining region master regulator for maleness turns on genes for production of male hormones

many effects = pleiotropy!

X chromosome other genes/traits beyond sex determination

mutations: hemophilia Duchenne muscular dystrophy color-blindness

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Sex-linked usually

means“X-linked”

more than 60 diseases traced to genes on X chromosome

Duchenne muscular dystrophyBecker muscular dystrophy

Ichthyosis, X-linkedPlacental steroid sulfatase deficiencyKallmann syndromeChondrodysplasia punctata, X-linked recessive

HypophosphatemiaAicardi syndromeHypomagnesemia, X-linkedOcular albinismRetinoschisis

Adrenal hypoplasiaGlycerol kinase deficiency

Incontinentia pigmentiWiskott-Aldrich syndromeMenkes syndrome

Charcot-Marie-Tooth neuropathyChoroideremiaCleft palate, X-linkedSpastic paraplegia, X-linked, uncomplicatedDeafness with stapes fixation

PRPS-related gout

Lowe syndrome

Lesch-Nyhan syndromeHPRT-related gout

Hunter syndromeHemophilia BHemophilia AG6PD deficiency: favismDrug-sensitive anemiaChronic hemolytic anemiaManic-depressive illness, X-linkedColorblindness, (several forms)Dyskeratosis congenitaTKCR syndromeAdrenoleukodystrophyAdrenomyeloneuropathyEmery-Dreifuss muscular dystrophyDiabetes insipidus, renalMyotubular myopathy, X-linked

Androgen insensitivity

Chronic granulomatous diseaseRetinitis pigmentosa-3

Norrie diseaseRetinitis pigmentosa-2

Sideroblastic anemiaAarskog-Scott syndrome

PGK deficiency hemolytic anemia

Anhidrotic ectodermal dysplasia

AgammaglobulinemiaKennedy disease

Pelizaeus-Merzbacher diseaseAlport syndrome

Fabry disease

Albinism-deafness syndrome

Fragile-X syndrome

Immunodeficiency, X-linked,with hyper IgM

Lymphoproliferative syndrome

Ornithine transcarbamylase deficiency

Human X chromosome

AP Biology

Map of Human Y chromosome?

< 30 genes on Y chromosome Sex-determining Region Y (SRY)

Channel Flipping (FLP)Catching & Throwing (BLZ-1)

Self confidence (BLZ-2)note: not linked to ability gene

Devotion to sports (BUD-E)

Addiction to death &destruction movies (SAW-2)

Scratching (ITCH-E)Spitting (P2E) linked

Inability to express affection over phone (ME-2) Selective hearing loss (HUH)

Total lack of recall for dates (OOPS)

Air guitar (RIF)

Yellow = heterochromatin

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Sex-linked traits summary X-linked

follow the X chromosomes males get their X from their mother trait is never passed from father to son

Y-linked very few genes / traits trait is only passed from father to son females cannot inherit trait

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Hemophilia

Hh x HHXHYXHXh

XHXh

XH

Xh

XHY

Y

XH

sex-linked recessive

XH Ymale / sperm

XH

Xh

fem

ale

/ eg

gs XHXH

XHXh

XHY

XhY

XHXH XHY

XHXh XhY

carrier disease

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X-inactivation Female mammals inherit 2 X chromosomes

one X becomes inactivated during embryonic development condenses into compact object = Barr body which X becomes Barr body is random

patchwork trait = “mosaic”

XHXh

XH

Xh

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X-inactivation & tortoise shell cat 2 different cell lines in cat

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Male pattern baldness Sex influenced trait

autosomal trait influenced by sex hormones age effect as well = onset after 30 years old

dominant in males & recessive in females B_ = bald in males; bb = bald in females

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Nature vs. nurture Phenotype is controlled by

both environment & genes

Color of Hydrangea flowers is influenced by soil pH

Human skin color is influenced by both genetics & environmental conditions

Coat color in arctic fox influenced by heat sensitive alleles

AP Biology Thanks as always to Kim Foglia

Mechanisms of Inheritance

How do we go from DNA to trait?

vs.?

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Mechanisms of inheritance What causes the differences in alleles

of a trait? yellow vs. green color smooth vs. wrinkled seeds dark vs. light skin sickle cell anemia vs. no disease

What causes dominance vs. recessive?

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Molecular mechanisms of inheritance Molecular basis of inheritance

genes code for polypeptides polypeptides are processed into proteins proteins function as…

enzymes structural proteins regulators

hormones gene activators gene inhibitors

proteinRNADNA trait

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How does dominance work: enzyme= allele coding for

functional enzymeprotein

= allele coding fornon-functional enzymeprotein

= 100% non-functional enzyme mutant trait is expressed

= 50% functional enzyme sufficient enzyme present normal trait is expressed normal trait is DOMINANT

= 100% functional enzyme normal trait is expressed

aa

Aa

AA

example: enzyme has incorrect structure at active site

carrier

homozygous

homozygous

heterozygous

dominant

recessive

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How does dominance work: structure= allele coding for

functional structural protein

= allele coding fornon-functional structural protein

= 100% non-functional structure mutant trait is expressed

= 50% functional structure 50% proteins malformed mutant trait is expressed mutant trait is DOMINANT

= 100% functional structure normal trait is expressed

AA

Aa

aahomozygous

homozygous

heterozygous

recessive

dominant

example: malformed channel protein, “stuck open”example: malformed receptor protein, “stuck on”

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Prevalence of dominance Because an allele is dominant

does not mean… it is better, or it is more common

Polydactylydominant allele

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Polydactyly

recessive allele far more common than dominant only 1 individual out of 500

has more than 5 fingers/toes so 499 out of 500 people are

homozygous recessive (aa)

the allele for >5 fingers/toes is DOMINANT & the allele for 5 digits is recessive

individuals are born with extra fingers or toes

AP Biology

Hound Dog Taylor

AP Biology Thanks as always to Kim Foglia

Any Questions?

AP Biology

How does dominance work: enzyme= allele coding for

functional enzymeprotein

= allele coding fornon-functional enzymeprotein

= 100% non-functional enzyme mutant trait is expressed

= 50% functional enzyme sufficient enzyme present normal trait is expressed normal trait is DOMINANT

= 100% functional enzyme normal trait is expressed

aa

Aa

AA

example: enzyme has incorrect structure at active site

carrier

homozygous

homozygous

heterozygous

___________

___________

AP Biology

How does dominance work: structure= allele coding for

functional structural protein

= allele coding fornon-functional structural protein

= 100% non-functional structure mutant trait is expressed

= 50% functional structure 50% proteins malformed mutant trait is expressed mutant trait is DOMINANT

= 100% functional structure normal trait is expressed

AA

Aa

aahomozygous

homozygous

heterozygous

___________

___________

example: malformed channel protein, “stuck open”example: malformed receptor protein, “stuck on”